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A Light‐Triggered Mesenchymal Stem Cell Delivery System for Photoacoustic Imaging and Chemo‐Photothermal Therapy of Triple Negative Breast Cancer
Advanced Science ( IF 15.1 ) Pub Date : 2018-08-24 , DOI: 10.1002/advs.201800382
Chang Xu 1 , Qishuai Feng 1 , Haocheng Yang 1 , Guangxue Wang 2 , Liqun Huang 3 , Qianwen Bai 1 , Chuyi Zhang 2 , Yilong Wang 1 , Yingna Chen 4 , Qian Cheng 4 , Mengwei Chen 1 , Yu Han 5 , Zuoren Yu 2 , Maciej S Lesniak 5 , Yu Cheng 1
Affiliation  

Targeted therapy is highly challenging and urgently needed for patients diagnosed with triple negative breast cancer (TNBC). Here, a synergistic treatment platform with plasmonic–magnetic hybrid nanoparticle (lipids, doxorubicin (DOX), gold nanorods, iron oxide nanocluster (LDGI))–loaded mesenchymal stem cells (MSCs) for photoacoustic imaging, targeted photothermal therapy, and chemotherapy for TNBC is developed. LDGI can be efficiently taken up into the stem cells with good biocompatibility to maintain the cellular functions. In addition, CXCR4 on the MSCs is upregulated by iron oxide nanoparticles in the LDGI. Importantly, the drug release and photothermal therapy can be simultaneously achieved upon light irradiation. The released drug can enter the cell nucleus and promote cell apoptosis. Interestingly, light irradiation can control the secretion of cellular microvehicles carrying LDGI for targeted treatment. A remarkable in vitro anticancer effect is observed in MDA‐MB‐231 with near‐infrared laser irradiation. In vivo studies show that the MSCs‐LDGI has the enhanced migration and penetration abilities in the tumor area via both intratumoral and intravenous injection approaches compared with LDGI. Subsequently, MSCs‐LDGI shows the best antitumor efficacy via chemo‐photothermal therapy compared to other treatment groups in the TNBC model of nude mice. Thus, MSCs‐LDGI multifunctional system represents greatly synergistic potential for cancer treatment.

中文翻译:

用于三阴性乳腺癌光声成像和化学光热治疗的光触发间充质干细胞递送系统

对于诊断为三阴性乳腺癌(TNBC)的患者来说,靶向治疗极具挑战性且迫切需要。这里,一个具有等离子磁性混合纳米颗粒(脂质、阿霉素(DOX)、金纳米棒、氧化铁纳米簇(LDGI))的协同治疗平台,负载间充质干细胞(MSC),用于光声成像、靶向光热治疗和 TNBC 化疗已开发。LDGI可有效被干细胞吸收,具有良好的生物相容性,维持细胞功能。此外,LDGI 中的氧化铁纳米颗粒上调了 MSC 上的 CXCR4。重要的是,光照射下可以同时实现药物释放和光热治疗。释放的药物可进入细胞核,促进细胞凋亡。有趣的是,光照射可以控制携带LDGI的细胞微载体的分泌,从而进行靶向治疗。在近红外激光照射下,MDA-MB-231 具有显着的体外抗癌作用。体内研究表明,与LDGI相比,MSCs-LDGI通过瘤内和静脉注射方式在肿瘤区域具有增强的迁移和渗透能力。随后,在裸鼠 TNBC 模型中,与其他治疗组相比,MSCs-LDGI 通过化学光热疗法显示出最佳的抗肿瘤功效。因此,MSCs-LDGI多功能系统在癌症治疗方面具有巨大的协同潜力。
更新日期:2018-08-24
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